Research Contributions of BCG Vaccination Programs: I. Tuberculin Allergy as a Family Trait

Objective: To determine frequency of scar formation and positive tuberculin conversion test following BCG vaccine administered within 0-28 days of life in children in 6 months to 6 years of age presenting at outpatient department of Fauji Foundation Hospital Lahore. Study Design: Descriptive case series. Place and Duration of Study: Outdoor Department of Pediatrics, Fauji Foundation Hospital, Lahore from 1st July 2020 to 30th December 2020. Methodology: Ninety seven children were included. Base line demographic information of patients (age, gender, weight on weight machine) was recorded. 0.5 ml BCG was administered in right arm. Tuberculin skin test was assessed as per operational definition. After 48 to 72 hours, scar formation was assessed after 1 month. Data regarding scar formation and positive tuberculin conversion test was recorded. Results: The mean age was 3.20±1.46 years, 39 (40.21%) were male whereas 58 (59.79%) were females. The scar formation following BCG vaccine administered within 0-28 days of life in children in 6 months to 6 years of age was 59 (60.82%) and positive tuberculin conversion test following BCG vaccine administered within 0-28 days of life in children in 6 months to 6 years was recorded in 47 (48.45%). Conclusion: Most babies have developed a post-vaccination scar. The combination of the BCG scar and the positive skin testing tuberculin was very important. The development of BCG scars had no effect on age or sex. Greater trials are advised in order to detect the true extent of the problem and to evaluate regularly the BCG vaccination programs. Keywords: Infants, Tuberculosis, BCG vaccination, Scar formation, Positive tuberculin conversion test

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Large-Scale Structure-Based Screening of Potential T Cell Cross-Reactivities Involving Peptide-Targets From BCG Vaccine and SARS-CoV-2

Frontiers in Immunology ◽

10.3389/fimmu.2021.812176 ◽

2022 ◽

Vol 12 ◽

Author(s):

Renata Fioravanti Tarabini ◽

Mauricio Menegatti Rigo ◽

André Faustino Fonseca ◽

Felipe Rubin ◽

Rafael Bellé ◽

...

Keyword(s):

T Cell ◽

Large Scale ◽

Vaccine Development ◽

Human Leukocyte ◽

Cross Reactivity ◽

Vaccination Programs ◽

Bcg Vaccination ◽

Leukocyte Antigens ◽

Infected Cells ◽

First Time

Although not being the first viral pandemic to affect humankind, we are now for the first time faced with a pandemic caused by a coronavirus. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been responsible for the COVID-19 pandemic, which caused more than 4.5 million deaths worldwide. Despite unprecedented efforts, with vaccines being developed in a record time, SARS-CoV-2 continues to spread worldwide with new variants arising in different countries. Such persistent spread is in part enabled by public resistance to vaccination in some countries, and limited access to vaccines in other countries. The limited vaccination coverage, the continued risk for resistant variants, and the existence of natural reservoirs for coronaviruses, highlight the importance of developing additional therapeutic strategies against SARS-CoV-2 and other coronaviruses. At the beginning of the pandemic it was suggested that countries with Bacillus Calmette-Guérin (BCG) vaccination programs could be associated with a reduced number and/or severity of COVID-19 cases. Preliminary studies have provided evidence for this relationship and further investigation is being conducted in ongoing clinical trials. The protection against SARS-CoV-2 induced by BCG vaccination may be mediated by cross-reactive T cell lymphocytes, which recognize peptides displayed by class I Human Leukocyte Antigens (HLA-I) on the surface of infected cells. In order to identify potential targets of T cell cross-reactivity, we implemented an in silico strategy combining sequence-based and structure-based methods to screen over 13,5 million possible cross-reactive peptide pairs from BCG and SARS-CoV-2. Our study produced (i) a list of immunogenic BCG-derived peptides that may prime T cell cross-reactivity against SARS-CoV-2, (ii) a large dataset of modeled peptide-HLA structures for the screened targets, and (iii) new computational methods for structure-based screenings that can be used by others in future studies. Our study expands the list of BCG peptides potentially involved in T cell cross-reactivity with SARS-CoV-2-derived peptides, and identifies multiple high-density “neighborhoods” of cross-reactive peptides which could be driving heterologous immunity induced by BCG vaccination, therefore providing insights for future vaccine development efforts.

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Tuberculosis versus COVID-19 Mortality: A New Evidence

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.5248 ◽

2020 ◽

Vol 8 (T1) ◽

pp. 179-183

Author(s):

Hayder Al-Momen ◽

Tareef Fadhil Raham ◽

Aqil Mohammad Daher

Keyword(s):

Immune Activation ◽

Latent Tuberculosis ◽

World Health ◽

Protective Mechanism ◽

Middle Income ◽

Vaccination Programs ◽

Bcg Vaccination ◽

Normal Individuals ◽

Health Organization ◽

Duration Of Protection

BACKGROUND: Coronavirus current pandemic (COVID-19) is the striking subject worldwide hitting countries in an unexplained non-universal pattern. Bacillus Calmette–Guérin (BCG) vaccine was an adopted recent justification depending on its non-specific immune activation properties. Still the problem of post-vaccine short duration of protection needs to be solved. The same protective mechanism was identified in active or latent tuberculosis (TB). For each single patient of active TB, there are about nine cases of asymptomatic latent TB apparently normal individuals living within the community without restrictions carrying benefits of immune activation and involved in re-infection cycles in an excellent example of repeated immunity training sessions of the whole community. AIM: We aimed to asses the correlation between TB burden and COVID-19 mortality in all affected countries having different BCG vaccination policies. METHODS: Publicly available data were extracted for 191 countries including population size, TB estimations, national BCG vaccination policy, the World Health Organization regions and economic classification, and COVID-19 mortality and number of cases. The analysis was performed using Spearman’s correlation test. RESULTS: Significant large negative correlation (−0.539, p < 0.001) was found between TB prevalence and COVID-19 mortality rate worldwide. Medium negative significant correlations were found between TB cases and COVID-19 mortality in the high and lower middle-income countries, and those having current BCG vaccination programs (−0.395, p = 0.001, −0.365, p = 0.015, and −0.476, p < 0.001, respectively). CONCLUSION: Countries with high TB prevalence have higher chances of protection against COVID-19 mortality through the theory of widely distributed natural immune activation within community. Confounders should be assessed separately.

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Research Contributions of BCG Vaccination Programs: II. Tuberculin Sensitivity at Different Altitudes of Residence

Public Health Reports (1896-1970) ◽

10.2307/4587901 ◽

1951 ◽

Vol 66 (44) ◽

pp. 1427 ◽

Cited By ~ 17

Author(s):

LeRoy E. Bates ◽

Thøger Busk ◽

Carroll E. Palmer

Keyword(s):

Vaccination Programs ◽

Bcg Vaccination ◽

Tuberculin Sensitivity ◽

Different Altitudes

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Impact of Duration of Cessation of Mass BCG Vaccination Programs on Covid -19 Mortality

10.1101/2020.08.20.20178889 ◽

2020 ◽

Cited By ~ 1

Author(s):

Tareef Fadhil Raham

Keyword(s):

Statistical Correlation ◽

P Value ◽

Confounding Factors ◽

Vaccination Programs ◽

Bcg Vaccination ◽

Screening Behavior ◽

Compound Model ◽

Back Ground ◽

Data Screening ◽

Stem Leaf

Back ground: BCG have heterogeneous immunity to certain pathogens other than Mycobacterium tuberculosis effect. At early times during COVID-19 pandemic heterogeneous immunity towards (SARS-CoV-2), was hypothesized and statistical correlation between of BCG vaccination practices and COVID-19 mortality variances among countries was statistically proved . These studies was criticized because of low evidence of such studies and possible confounding factors. For that reason this study was designed to look for impact of duration of cessation of BCG programs on Covid-19 mortality looking for the hypotheses by different design and looking forward to support previous studies. Methods: Total number of studied group is 14 countries which has stopped BCG vaccination programs. Through applying stem-leaf plot for exploring data screening behavior concerning Covid-19 Mortality for obsolescence duration of cessation of mass BCG vaccination programs, as well as (nonlinear regression of compound model) for predicted shape behavior for that group. Results: Slope value shows highly significant effectiveness of obsolescence of cessation of mass BCG vaccination programs on Covid -19 mortality at P-value<0.000. Obsolescence of duration of cessation of mass BCG vaccination programs has strongly negatively associated with Covid-19 mortality in countries which stopped BCG vaccination programs. Conclusion: The longer the cessation duration of BCG programs, the higher the Covid-19 mortality is, and vice versa.

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COVID-19 Death and BCG Vaccination Programs Worldwide

Tuberculosis and Respiratory Diseases ◽

10.4046/trd.2020.0063 ◽

2021 ◽

Vol 84 (1) ◽

pp. 13-21 ◽

Cited By ~ 4

Author(s):

Feras J. Jirjees ◽

Yahya H. Dallal Bashi ◽

Hala J. Al-Obaidi

Keyword(s):

Vaccination Programs ◽

Bcg Vaccination

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The association of Coronavirus Disease-19 mortality and prior bacille Calmette-Guerin vaccination: a robust ecological analysis using unsupervised machine learning

Scientific Reports ◽

10.1038/s41598-020-80787-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nathan A. Brooks ◽

Ankur Puri ◽

Sanya Garg ◽

Swapnika Nag ◽

Jacomo Corbo ◽

...

Keyword(s):

Machine Learning ◽

Population Level ◽

Ecological Analysis ◽

Bacille Calmette Guerin ◽

Vaccination Programs ◽

Bcg Vaccination ◽

Level Data ◽

Specific Modeling ◽

Related Mortality ◽

Country Specific

AbstractPopulation-level data have suggested that bacille Calmette-Guerin (BCG) vaccination may lessen the severity of Coronavirus Disease-19 (COVID-19) prompting clinical trials in this area. Some reports have demonstrated conflicting results. We performed a robust, ecologic analysis comparing COVID-19 related mortality (CRM) between strictly selected countries based on BCG vaccination program status utilizing publicly available databases and machine learning methods to define the association between active BCG vaccination programs and CRM. Validation was performed using linear regression and country-specific modeling. CRM was lower for the majority of countries with a BCG vaccination policy for at least the preceding 15 years (BCG15). CRM increased significantly for each increase in the percent population over age 65. A higher total population of a country and BCG15 were significantly associated with improved CRM. There was a consistent association between countries with a BCG vaccination for the preceding 15 years, but not other vaccination programs, and CRM. BCG vaccination programs continued to be associated with decreased CRM even for populations < 40 years old where CRM events are less frequent.

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SARS-CoV-2 Genetic Variability and Non-Specific Immunity Associated with the Use of Different BCG Strains—A Molecular and Clinical Approach

Vaccines ◽

10.3390/vaccines9060639 ◽

2021 ◽

Vol 9 (6) ◽

pp. 639

Author(s):

Jakub Kulus ◽

Magdalena Kulus ◽

Katarzyna Stefańska ◽

Jarosław Sobolewski ◽

Hanna Piotrowska-Kempisty ◽

...

Keyword(s):

Genetic Variability ◽

Infectious Agent ◽

Clinical Approach ◽

Immune Protection ◽

Vaccination Programs ◽

High Genetic Variability ◽

Bcg Vaccination ◽

Specific Immunity ◽

The United Kingdom ◽

Genetic Makeup

The effect of BCG vaccination against tuberculosis on the reduction in COVID-19 infection is related to the effect of the BCG vaccine on the immunomodulation of non-specific immunity. In the early stages of the pandemic, countries with universal BCG vaccination programs registered a low number of new cases of COVID-19, with the situation now reversed, as exemplified by India. The high genetic variability of SARS-CoV-2, a known characteristic of RNA viruses, causing the occurrence of SARS-CoV-2 variants may have led to the virus adapting to overcome the initial immune protection. The strains from the United Kingdom (B1.1.7), Brazil (B1.1.28 and B1.1.33), South Africa (B.1.351), and India (B.1.617) are characterized by a greater ability to spread in the environment, in comparison with the original infectious agent of SARS-CoV-2. It should be remembered that the large variation in the genetic makeup of SARS-CoV-2 may result in future changes in its pathogenicity, immunogenicity and antigenicity, and therefore it is necessary to carefully study the mutations occurring within the virus to determine whether the current vaccines will remain effective. However, most studies show that monoclonal antibodies produced after vaccination against COVID-19 are effective against the newly developed variants.

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The association of Coronavirus Disease-19 mortality and prior bacille Calmette-Guerin vaccination: a robust ecological evaluation using unsupervised machine learning

10.21203/rs.3.rs-35340/v1 ◽

2020 ◽

Author(s):

Nathan A Brooks ◽

Ankur Puri ◽

Sanya Garg ◽

Swapnika Nag ◽

Noshir Kaka ◽

...

Keyword(s):

Machine Learning ◽

Population Level ◽

Bacille Calmette Guerin ◽

Ecological Evaluation ◽

Vaccination Programs ◽

Bcg Vaccination ◽

Level Data ◽

Specific Modeling ◽

Related Mortality ◽

Country Specific

Abstract Population-level data have suggested that bacille Calmette-Guerin (BCG) vaccination may lessen the severity of Coronavirus Disease-19 (COVID-19) prompting clinical trials in this area. Some reports have demonstrated conflicting results. We performed a robust, ecologic analysis comparing COVID-19 related mortality (CSM) between strictly selected countries based on BCG vaccination program status utilizing publicly available databases and machine learning to define the association between active BCG vaccination programs and CSM. Validation was performed using linear regression and country-specific modeling. CSM was lower for 80% of similarly clustered countries with a BCG vaccination policy for at least the preceding 15 years (BCG15). CSM increased significantly for each increase in the percent population over age 65. The total population of a country and BCG15 were significantly associated with improved CSM. There was a consistent association between countries with a BCG vaccination for the preceding 15 years, but not other vaccination programs, and CSM.

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Isolated Strains of Nontuberculous Mycobacterium Interfere with Immune Responses Associated with Mycobacterium Bovis BCG Vaccination

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.884-885.450 ◽

2014 ◽

Vol 884-885 ◽

pp. 450-454

Author(s):

Chun Fang Wang ◽

Hua Rui Qi ◽

Xiu Yun Jiang ◽

Hong Xia Ma ◽

Ai Dong Qian ◽

...

Keyword(s):

Immune System ◽

Mycobacterium Bovis ◽

Growth Characteristics ◽

Nontuberculous Mycobacterium ◽

Murine Models ◽

Vaccination Programs ◽

Mycobacterium Bovis Bcg ◽

Bcg Vaccination ◽

Environmental Mycobacteria ◽

Mycobacterial Antigens

Prior exposure of a vaccine to certain species of environmental mycobacteria can prime the immune system against common mycobacterial antigens, which can in turn reduce the subsequent efficacy of live attenuated mycobacterial vaccines (such as Mycobacterium bovis BCG), in both human and livestock vaccination programs. In this study, five strains of nontubeculous mycobacterium, all isolated from lymphonodi mandibulares and lymphonodi mesenterici samples of swine and cattle, were investigated to determine their growth characteristics and effects on the immune system in murine models. Markedly, different effects on the immune system were observed. The different results may be linked to the inherent growth characteristics of the five strains, The implications of these findings for BCG vaccination protocols are discussed.

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